Molecular imaging of macrophages in atherosclerotic plaques using bimodal PEG-micelles

Authors

  • Willem J. M. Mulder,

    1. Biomedical NMR, Department of Biomedical Engineering, Eindhoven University of Technology, Eindhoven, The Netherlands
    2. Institute for Translational and Molecular Imaging, Department of Radiology, Mount Sinai School of Medicine, New York, New York, USA
    3. Eva and Morris Feld Estate Imaging Science Laboratories, Department of Radiology, Mount Sinai School of Medicine, New York, New York, USA
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  • Gustav J. Strijkers,

    1. Biomedical NMR, Department of Biomedical Engineering, Eindhoven University of Technology, Eindhoven, The Netherlands
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  • Karen C. Briley-Saboe,

    1. Institute for Translational and Molecular Imaging, Department of Radiology, Mount Sinai School of Medicine, New York, New York, USA
    2. Eva and Morris Feld Estate Imaging Science Laboratories, Department of Radiology, Mount Sinai School of Medicine, New York, New York, USA
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  • Juan C. Frias,

    1. Institute for Translational and Molecular Imaging, Department of Radiology, Mount Sinai School of Medicine, New York, New York, USA
    2. Eva and Morris Feld Estate Imaging Science Laboratories, Department of Radiology, Mount Sinai School of Medicine, New York, New York, USA
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  • Juan Gilberto S. Aguinaldo,

    1. Institute for Translational and Molecular Imaging, Department of Radiology, Mount Sinai School of Medicine, New York, New York, USA
    2. Eva and Morris Feld Estate Imaging Science Laboratories, Department of Radiology, Mount Sinai School of Medicine, New York, New York, USA
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  • Esad Vucic,

    1. Institute for Translational and Molecular Imaging, Department of Radiology, Mount Sinai School of Medicine, New York, New York, USA
    2. Eva and Morris Feld Estate Imaging Science Laboratories, Department of Radiology, Mount Sinai School of Medicine, New York, New York, USA
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  • Vardan Amirbekian,

    1. Institute for Translational and Molecular Imaging, Department of Radiology, Mount Sinai School of Medicine, New York, New York, USA
    2. Eva and Morris Feld Estate Imaging Science Laboratories, Department of Radiology, Mount Sinai School of Medicine, New York, New York, USA
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  • Cheuk Tang,

    1. Institute for Translational and Molecular Imaging, Department of Radiology, Mount Sinai School of Medicine, New York, New York, USA
    2. Eva and Morris Feld Estate Imaging Science Laboratories, Department of Radiology, Mount Sinai School of Medicine, New York, New York, USA
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  • Patrick T. K. Chin,

    1. Laboratory of Macromolecular and Organic Chemistry, Eindhoven University of Technology, Eindhoven, The Netherlands
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  • Klaas Nicolay,

    1. Biomedical NMR, Department of Biomedical Engineering, Eindhoven University of Technology, Eindhoven, The Netherlands
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  • Zahi A. Fayad

    Corresponding author
    1. Institute for Translational and Molecular Imaging, Department of Radiology, Mount Sinai School of Medicine, New York, New York, USA
    2. Eva and Morris Feld Estate Imaging Science Laboratories, Department of Radiology, Mount Sinai School of Medicine, New York, New York, USA
    • Imaging Science Laboratories, Mount Sinai School of Medicine, One Gustave L. Levy Place, Box 1030, New York, NY 10029
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Abstract

Pegylated, fluorescent, and paramagnetic micelles were developed. The micelles were conjugated with macrophage scavenger receptor (MSR)-specific antibodies. The abdominal aortas of atherosclerotic apoE-KO mice were imaged with T1-weighted high-resolution MRI before and 24 h after intravenous administration of the contrast agent (CA). Pronounced signal enhancement (SE) (up to 200%) was observed for apolipoprotein E knockout (apoE-KO) mice that were injected with MSR-targeted micelles, while the aortic vessel wall of mice injected with nontargeted micelles showed little SE. To allow fluorescence microscopy and optical imaging of the excised aorta, the micelles were made fluorescent by incorporating either a quantum dot (QD) in the micelle corona or rhodamine lipids in the micelle. Ultraviolet (UV) illumination of the aorta allowed the identification of regions with high macrophage content, while MSR-targeted rhodamine micelles could be detected with fluorescence microscopy and were found to be associated with macrophages. In conclusion, this study demonstrates that macrophages in apoE-KO mice can be effectively and specifically detected by molecular MRI and optical methods upon administration of a pegylated micellar CA. Magn Reson Med 58:1164–1170, 2007. © 2007 Wiley-Liss, Inc.

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